TY - JOUR
T1 - Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma
AU - Hes, Cecilia
AU - Desilets, Antoine
AU - Tonneau, Marion
AU - El Ouarzadi, Omar
AU - De Figueiredo Sousa, Marina
AU - Bahig, Houda
AU - Filion, Édith
AU - Nguyen-Tan, Phuc Felix
AU - Christopoulos, Apostolos
AU - Benlaïfaoui, Myriam
AU - Derosa, Lisa
AU - Alves Costa Silva, Carolina
AU - Ponce, Mayra
AU - Malo, Julie
AU - Belkad, Wiam
AU - Charpentier, Danielle
AU - Aubin, Francine
AU - Hamilou, Zineb
AU - Jamal, Rahima
AU - Messaoudene, Meriem
AU - Soulières, Denis
AU - Routy, Bertrand
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Objectives: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. Materials and methods: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. Results: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0–10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8–9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1–2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1–2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. Conclusion: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
AB - Objectives: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. Materials and methods: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. Results: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0–10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8–9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1–2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1–2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. Conclusion: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
KW - Chemoradiation therapy
KW - Head and neck squamous cell cancer
KW - Microbiome
KW - Mucositis
UR - http://www.scopus.com/inward/record.url?scp=85178063181&partnerID=8YFLogxK
U2 - 10.1016/j.oraloncology.2023.106623
DO - 10.1016/j.oraloncology.2023.106623
M3 - Article
C2 - 38006691
AN - SCOPUS:85178063181
SN - 1368-8375
VL - 148
JO - Oral Oncology
JF - Oral Oncology
M1 - 106623
ER -